Takotsubo cardiomyopathy in the setting of severe hyponatremia and beer potomania: A case report

Abstract Takotsubo cardiomyopathy (TC), an acute cardiac event is often associated with acute emotional stress, usually in the setting of cardiovascular risk factors. This case report attempts to review one of the triggers of TC beer potomania‐induce hyponatremia with imaging findings that shows the link between severe hyponatremia and TC.


| BACKGROUND
Takotsubo cardiomyopathy (TC), first described in Japan in 1990, is an acute cardiac condition that involves transient systolic dysfunction due to ballooning of the apex and/or mid segments of the left ventricle. 1 TC is also known as "apical ballooning syndrome," "stress-induced cardiomyopathy," "broken heart syndrome," and "ampulla cardiomyopathy". The name Takotsubo was derived from the Japanese word for octopus emblematic of the appearance of the left ventricle on ventriculography during an acute attack. The typical TC includes apical ballooning during systole due to hypokinesis or akinesis of the apex or mid ventricle and hyperkinesis of the basal walls. Atypical variants of TC include hypokinesis of the mid-ventricle alone, 2 hypokinesis of the base, and global hypokinesis. 3 Takotsubo cardiomyopathy patients are typically seen in postmenopausal Asian or Caucasian women. Gianni et al reported that 88.8% of 286 reported TC patients were women. The mean age ranges from 61 to 76 years. 4 The exact prevalence of TC is unknown, but researchers have reported that 1.7-2.2% of suspected ACS patients have TC. [5][6][7] TC is usually but not always brought on by an acute medical illness or an intense mental or physical stressor. 8 TC patients typically present with symptoms similar to ACS, including chest pain with echocardiographic changes and elevated cardiac markers. However, upon angiography, no significant coronary artery obstruction is appreciated. Sadamatsu et al reported two cases with apical wall abnormalities and reduced coronary flow without coronary stenosis. 9 We report a case of Takotsubo cardiomyopathy in a patient who initially presented with severe hyponatremia from beer potomania. This patient did not present with chest pain; however, the apical ballooning and negative coronary artery disease were discovered on left heart catherization and ventriculogram.

| CASE PRESENTATION
A 56-year-old African American male with medical history significant for hypertension, hyperlipidemia, and alcohol dependence who presented with incoherent speech with altered mentation. He reported dyspnea with mild exertion. He denied chest pain, orthopnea, paroxysmal nocturnal dyspnea, or pedal swelling. He has been binge drinking several cans of beer, about 24 of 24 -Oz can, prior to presentation. This was, following, a sudden incarceration and imprisonment of his wife. Patient had his last drink 5 h prior to presentation to the emergency room.
Examination revealed a disheveled middle-age African American male who was confused and inebriated. His Vital signs revealed blood pressure 129/67 mmHg, pulse 73beats/min, and body temperature 99.4 F. He was somnolent but easily arousable and oriented to person and place but not to time or situation. Neurologic examination showed no focal neurological deficits. The rest of his physical examination yielded no addition findings. Laboratory investigations including biochemical and hematologic results obtained in the ER are listed below (Table 1). This revealed serum sodium 102 mmol/L, serum osmolality 245 mOsm/L, urine osmolality 44 mOsm/L, urine sodium 7 mmol/L, blood alcohol level 221 mg/dL, and creatine kinase 7810 units/L. Random urine drug screen was positive for opiates. Initial electrocardiogram showed normal sinus rhythm ( Figure 1). Chest X-ray showed no acute cardiopulmonary process ( Figure 2). About 45 min after presentation at the emergency department, he experienced violent incessant episodes of generalized clonic-tonic seizure episode involving all limbs. This was concerning for status epilepticus and required sedation with phenobarbital and intubation for airway protection at the medical intensive care unit at our community hospital. Nephrology, critical care, and neurology consultation were subsequently placed.
Patient was given hypertonic saline with close monitoring of his serum sodium and electrolytes. The rise in serum sodium was 0.5-1 mmol/L/h, and serum sodium gradually improved to 120 over 2 days. The patient's chest X-ray demonstrated possible right middle lobe pneumonia, and he was started on broad-spectrum antibiotics of ceftriaxone and azithromycin intravenously. The patient continued to be on mechanical ventilation and multiple attempts at extubating failed.
Over the next 24-48 h, a change was noted on telemetry monitoring concerning for ST elevation and a 12-lead electrocardiogram showed early repolarization abnormalities in the left lateral leads (Figure 3). Follow-up cardiac enzymes done showed troponin of 4.30 mg/ml, creatine kinase-MB 50 U/L, and creatine kinase 1293 U/L." The ST elevations did not qualify for classification as STEMI; however, he required urgent treatment for NSTE-ACS. The patient was, subsequently transferred to a neighboring hospital with percutaneous coronary intervention and cardiac catheterization capability.
He stayed on mechanical ventilation several days. Echocardiogram done prior to the left heart catherization showed left ventricular ejection fraction of 30% with severe mid-distal and apical hypokinesis and ballooning, and relaxation abnormality of left ventricular hypertrophy with mild concentric left ventricular hypertrophy was also appreciated (Video S1). The patient received aspirin, metoprolol, and lisinopril orally with heparin intravenously as medical therapy.
The left heart catheterization (LHC) done showed no evidence of obstructive CAD (Figure 4). There was no evidence of coronary vasospasm. LV angiogram showed apical ballooning and hypokinesis of anteroseptal left ventricle concerning for Takotsubo cardiomyopathy ( Figure 5). The patient was monitored closely after the LHC. Troponin peaked at 33.0 mg/ml and subsequently trended down 0.04 mg/ml, 3 days after the LHC.
He remained on hypertonic saline with increases of his serum sodium to 123 mmol/L. The hypertonic saline was stopped when his serum sodium increased to 129 mmol/L. The sodium remained stable at 128-130 mmol/L. He was successfully extubated, after 4 days of mechanical ventilation. His mental status slowly improved and began to respond to commands. Patient made steady improvement in his clinical condition, antibiotics was discontinued and was discharge after 6 days of hospital stay.
An echocardiogram done a month post admission during a follow-up clinic visit to our hospital showed left ventricular ejection fraction of 55% with resolution of apical hypokinesis and ballooning (Video S2).

| DISCUSSION
The patient's initial presentation of a low serum sodium of 101 mmol/L raised the possibility of number of differential diagnoses including syndrome of inappropriate anti diuretic hormone (SIADH), dehydration, congestive heart failure, chronic kidney disease, cerebral wasting syndrome, psychogenic polydipsia, and beer potomania. Low urine osmolarity F I G U R E 1 Initial Electrocardiogram showing normal sinus rhythm

F I G U R E 2
Initial Chest x-ray showing no acute cardiopulmonary process and low urine sodium levels excluded dehydration, SIADH, and cerebral wasting syndrome as the cause of this patient's hyponatremia. 10 The patient's denial of drinking excessive water also ruled out psychogenic polydipsia. This patient's noncontributory initial physical examination, along with chest X-ray, without any acute intrathoracic process with a normal BNP and renal function essentially ruled out congestive heart failure and renal insufficiency.
His history of alcohol abuse, including clinical presentation of lethargy and disheveled appearance, along with his laboratory work up of low serum osmolarity, urine osmolarity, and low urine sodium results and absence of possible explanation, led us to the possibility of beer potomania accounting for the patient's hyponatremia. Our eventual working diagnosis of the patient's hyponatremia was likely related to alcohol, and hence, the patient possibly had beer potomania evidenced by low urine sodium and severe hyponatremia. This together led to the status epilepticus our patient experienced. We hypothesize that his severe hyponatremia may have cause the Takotsubo cardiomyopathy (TC), especially in the context of epileptic seizures. The TC evidenced by the absence of coronary artery stenosis on LHC and presence of apical ballooning on ventriculogram and echocardiogram. This was buttressed by a low left ventricular ejection fraction of 30% and its eventual improvement to 55% over a relatively short period of time of a month.
The pathogenesis of TC is not fully understood, but the proposed mechanisms include endogenous catecholamine excess, multivessel coronary artery vasospasm, and microvascular dysfunction. The most favored mechanism is endogenous catecholamine excess leading to microvascular spasm or dysfunction resulting in myocardial stunning. 11 Others have also discussed a direct toxicity of cardiomyocyte from the large amount of circulating catecholamines. 12 In support of the endogenous catecholamine excess hypothesis, a mouse model showed that a high level of epinephrine had negatively inotropic effect on cardiomyocytes due to a switch from beta-2 adrenoceptor Gs protein signaling to Gi protein signaling. It is speculated that the effect is greatest on the apex of the myocardium because of a higher density of beta-2 adrenoceptors. 13 Additionally, Ellison et al found that high doses of isoproterenol cause diffuse death of myocytes while sparing cardiac stem cells in rats allowing for rapid recovery of the myocardium. 14 Akashi et al in another study reported that TC patients had an increased myocardial 123 I-metaodobenzlguanide ( 123 I-MBG) washout rate which indicates an increased norepinephrine release from sympathetic nerve endings or increased clearance of 123 I-MBG by extra neural tissues. Ultimately, the increased wash out rate correlated to increased plasma norepinephrine levels in TC patients. 15 There are a few case reports of TC in the setting of moderate to severe hyponatremia described in the body of literature. 16,17,[18][19][20][21] Hyponatremia has not been thought to be linked to Takotsubo cardiomyopathy but perhaps may have an indirect causal relationship. The prevailing theory of this indirect causal relationship is a stress-induced catecholamine storm causing a direct toxic effect on the myocardium or indirect effect by coronary vasculature constriction. The mechanistic connection is still not clear; however, it has been suggested that hyponatremia could interfere with myocardial inotropy by modifying the cardiomyocytic sodium-calcium exchange pump resulting in myocardial swelling associated with hypotonicity. 16 Indeed, transient positive inotropic effects on the myocardium were observed in rat hearts, and the degree of positive inotropy correlated with the degree of hyponatremia. 22 There have been cases reported of Takotsubo cardiomyopathy in the setting of "isolated hyponatremia," and it has been suggested that in post-menopausal women presenting with acute coronary syndrome-like symptoms and hyponatremia, Takotsubo cardiomyopathy should be considered within the differential diagnoses. 17 Takotsubo cardiomyopathy arising as a direct consequence of hyponatremia is an unexplored mechanism for this poorly understood disease process. The prevailing theories for the F I G U R E 5 Ventriculogram imaging showing the apical and mid segment left ventricular. Akinesis and ballooning, taking the shape of the proverbial Japanese octopus, Takotsubo cardiomyopathy. Left image: apical left ventricular Akinesis and ballooning. Right image: Mid-segment left ventricular ballooning pathogenesis of TC involve excessive catecholamine action on the myocardium causing stunning either directly or through ischemia by causing multivessel epicardial or microvascular spasm. 23 There has also been a long-recognized connection between TC and stress, particularly strong emotional stress, which suggests that there may be a neurohumoral connection that precipitates TC. Interestingly, TC has been found in cases of subarachnoid hemorrhage and stroke, and neurologists have advanced the idea "neurogenic stunning" to describe this reversible cardiomyopathy in the setting of brain injury in the absence of coronary artery disease 23 Norepinephrine release in the myocardium is increased as a result of hypothalamic ischemia from a subarachnoid hemorrhage and may be the cause of the myocardial injury observed. 24 Furthermore, this neurogenic stunning effect is dampened when there is a disruption of neural innervation of the myocardium as in diabetes or heart transplant. 25 Neurocardiac lesions also occur in adrenalectomized animals, but to a lesser extent, further strengthening the neurogenic stunning theory. 26 Although ischemia as a direct cause of TC is still being debated, the dysfunctional myocardium in TC follows a neural rather than vascular distribution, as there is a much higher concentration of adrenergic receptors in areas around myocardial arterioles than in areas adjacent to epicardial coronary arteries. 27

| CONCLUSION
Takotsubo cardiomyopathy's preferential effects on the sub-endocardial myocytes manifest as an increased propensity for arrhythmia; this combined with excessive catecholamines, which can induce arrhythmia even in healthy myocardium, may be a major cause of sudden death in neurologic disease including subarachnoid hemorrhage, stroke, head trauma, and increased intracranial pressure.
With the wealth of evidence connecting the brain's effect on the heart, perhaps hyponatremia indirectly causes TC by first causing cerebral edema. The resulting neurological disturbance results in excessive catecholamine action on the myocardium which manifests as TC.